Does infertility treatment put women at higher risk of cancers?

Many patients ask me if IVF treatment leads to a higher risk of cancers, especially in breasts and ovaries. As per the latest published scientific literature on this subject, there is no real evidence to link IVF with higher risk of cancers among these women.

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As an infertility specialist, I am required to counsel mcancery patients about potential complications of fertility treatment. One of the most often asked question is if infertility treatments put the women at a higher risk of cancers.

Fertility drugs like clomiphene citrate and hormones used for ovarian stimulation & assisted reproductive technologies like IVF and ICSI have all been implicated to causes various cancers among women, including not only cancers of cervix, uterus, ovaries and breast, but also melanoma and cancers of the central nervous system.

A simple answer to this question is that as per the latest studies, there is no conclusive evidence to suggest a higher risk of invasive cancers in women receiving infertility treatment.

Why has infertility treatment been linked with higher risk of cancers?

There are multiple theories as to why fertility treatment may increases the risk of cancer in women.

  1. Hormonal treatment with Clomiphene and Gonadotropins causes cancers because elevated levels of estrogen and progesterone hormones can trigger carcinogenic activity in the ovarian , uterine and breast tissues
  2. Ovarian enlargement due to development of multiple follicles causes trauma to the ovaries, which may result in carcinogenesis.
  3. Injury to ovaries resulting from multiple needle punctures made during egg retrieval has also been suggested to cause cancers of ovaries.

However, at the same time, it has also been suggested that infertile and nulliparous women are inherently at an increased risk of certain cancers so actually infertility treatment may not be the cause of cancers in these women.

What does the scientific evidence tell us?

Extensive research has been conducted on this subject, but the results so far have been pretty inconclusive. We need to appreciate that it is indeed difficult to study direct relationship between cancers in women and infertility treatment because many of these cancers appear many years after the treatment/ causative injury. Therefore, large populations have to be studied over a long period of time in order to arrive at any meaningful conclusions regarding the relationship between fertility treatment and cancers.

Of all the cancers suspected to be associated with infertility treatment, cancers in ovaries are most often linked to the infertility treatment. The overall evidence in this regard is mixed. While some studies have found the risk of ovarian cancers to be higher in women with a history of fertility treatment, others have ruled any such association out.

A research group from Israel retrospectively studied possibility of such an association in over 106,000 women, who had delivered between 1998 and 2013.1 The researchers found that women with conceived with IVF treatment had a significantly increased risk of being diagnosed with ovarian and uterine cancers as compared to women who had conceived either naturally or using ovulation induction. However, another study of over 87,000 women from Israel only conducted around the same time did not find any significant relationship between IVF exposure and risks of breast, endometrial, or ovarian cancers.2

In a population based cohort study of 812,986 women from Norway, who had delivered between 1984 and 2010, the researchers tried to assess the overall risk of cancers and specifically of cancers of cervix, uterus, ovary, thyroid, the central nervous system and melanoma among the women who had conceived using ART. 3 They found that the overall risk of cancers was not higher among the women conceiving using ART and delivering at least one baby. Although there was a hint of higher incidence of some cancers among women undergoing IVF, this could not be statistically proven owing to the weak nature of this kind of population based study.

A Cochrane review of 25 studies (consisting of 11 case-control studies and 14 cohort studies) covering 182,972 women did not find any convincing evidence supporting an increased risk of invasive ovarian tumors with fertility drug treatment. However, the researchers concluded that there may be an increased risk of borderline ovarian tumors in subfertile women treated with IVF.4

Cancer of the breast is the second most commonly discussed cancer that is assumed to be linked with hormonal treatment for infertility. Large studies and meta-analyses have not found any significant correlation between treatment for infertility and breast cancer. 5,6 While some studies have suggested that the risk of breast cancer increases after exposure to ovulation inducing agents (especially clomiphene citrate)6, many other studies do not support such an association.5 Therefore, I don’t advocate long term administration of Clomiphene, as the risk of breast cancer is not fully ruled out with its long term use.

Conclusion

Overall we can say that on the basis of existing scientific evidence, there is no conclusive proof of a causal link between ovarian and breast cancers and fertility treatment. Therefore, treatment of infertility using hormones and ART is by and large safe. The cancers of ovary and breast detected among women with history of treatment for infertility are more likely to be related to their infertile status than to the effect of fertility drugs. However, we must keep in mind that majority of the available studies on this subject suffer from methodological limitations and therefore cannot be fully relied upon. Further research on this subject will certainly enlighten us more on the possibility of any such association.

References

1.       The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up. Kessous et al. J Cancer Res Clin Oncol. 2016 Jan;142(1):287-93.

2.       In vitro fertilization and risk of breast and gynecologic cancers: a retrospective cohort study within the Israeli Maccabi Healthcare Services. Brinton et al. Fertil Steril. 2013 Apr;99(5):1189-96.

3.       Cancer risk among parous women following assisted reproductive technology. Reigstad et al. Hum Reprod. 2015 Aug;30(8):1952-63.

4.       Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility. Rizzuto I, Behrens RF, Smith LA. Cochrane Database Syst Rev. 2013 Aug 13;8:CD008215.

5.       IVF and breast cancer: a systematic review and meta-analysis. Sergentanis et al. Hum Reprod Update. Sergentanis et al. 2014 Jan-Feb;20(1):106-23.

6.       Breast cancer incidence after hormonal treatments for infertility: systematic review and meta-analysis of population-based studies. Gennari et al. Breast Cancer Res Treat. 2015 Apr;150(2):405-13.

For further information or queries on this subject, please write to me at ivfgurgaon@gmail.com.

Dr Parul Katiyar

Author: Dr Parul Katiyar MD (Infertility & Reproductive Medicine)

Senior Consultant Infertility and Reproductive Medicine Nova IVI Fertility Block B 2/1A, Africa Avenue, Safdarjung Enclave, RK Puram, Sector 2, New Delhi, Delhi 110029

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